One of the most exciting recent discoveries in pain research is that interactions between neurons and glial cells are critically involved in the establishment and maintenance of complex pain syndromes. While many studies have now shown the importance of such interactions in the spinal cord in relation to pain associated with nerve injury, much less is known about the significance of neuron-glial cell relations outside of the spinal cord where primary sensory neurons are located. Primary sensory neurons are the first neuron to sense painful stimuli and they are the ones damaged when there is a nerve injury. For sensation from the face the primary sensory neurons are located in the trigeminal ganglia and each neuron is surrounded by a unique type of glial cell called the satellite cell. After nerve injury both neurons their surrounding satellite cells undergo profound changes. One of the key roles of satellite cells is to ensure that constant levels of ions such as potassium are maintained around neurons. This occurs through the uptake and release of extracellular potassium through ionic channels in satellite cell membranes and redistribution of potassium between satellite cells via gap junctions. Neurons can directly affect these events by releasing neurotransmitters that reach satellite cells. It is likely that perturbation of the satellite cells, or the communication between satellite cells and neurons, will significantly change the ionic equilibrium in the trigeminal ganglion thereby playing a role in nerve injury pain. To study the influence of ionic changes on nerve injury pain, we propose to alter the expression of specific genes (one at the time) in satellite cells using a novel technique called RNA interference. Using this technique we are able to silence individual genes and observe the resulting effect on behavior and molecular adaptations in the trigeminal ganglion. The genes that we will target are related to potassium channels found only on satellite cells, gap junctions, and proteins in satellite cells on which neurotransmitters act. These studies will serve to establish the role of neuron-glial cell communication in facial neuropathic pain. By focusing on specific genes, we will further the understanding of the complex events that occur following nerve injury resulting in neuropathic pain as well as define targets for clinical intervention to reduce facial pain. This research looks nerve cells and the cells that surround them to understand what changes take place in these cells that result in a person feeling pain after an injury. We are specifically interested in the neurons that are involved in facial pain. Our aim is to find the key changes that give rise to pain in order to develop new treatments that will relieve pain without unwanted side effects. [unreadable] [unreadable] [unreadable]